This study investigates the feasibility of using live attenuated Salmonella as an oral vaccine vector for the delivery of human immunodeficiency virus antigens. Salmonella is promising as a candidate vaccine vector for several reasons. First, this organism elicits both systemic and mucosal immune responses. As most cases of HIV are sexually transmitted, mucosal immunity is likely to be critical in preventing infection. Second, foreign genes cloned into attenuated Salmonella vaccine strains have already been shown to elicit immune responses to viral, bacterial, fungal, and parasitic antigens in animal models. Third, an orally administered vaccine offers praCtical and financial advantages over parenterally administered vaccines. The primary objective of this study is to develop a strain of attenuated Salmonella stably expressing the HIV-1 gpl20 envelope protein. The candidate vaccine will be administered orally to BALB/c mice, and assessed for its ability to elicit humoral and cellular immune responses in both the systemic and mucosal compartments. The secondary objective is to delineate variables of antigen expression (such as plasmid copy number, mode of foreign gene regulation) important in the host immune response to Salmonella. The third objective of this project is to address the areas of oral Salmonella vaccine technology, and mucosal immunity, about which little is known. Such knowledge has potential for widespread application beyond the realm of HIV prevention.